Improved viral screening assays and more intensive questioning of donors for high-risk behaviors have resulted in dramatic declines in the rates of transfusion-transmitted hepatitis and AIDS. Nonetheless, there is need for continued vigilance of the safety of blood supply. This study will enroll blood donors and prospectively followed blood recipients in order to: 1) establish ongoing surveillance of the incidence of breakthrough infections from transfusion-transmitted agents for which there are existing donor-screening assays (e.g. HBV, HCV, HIV, human T cell lymphotropic virus HTLV); 2) monitor the transfusion risk of established infectious agents that are not routinely screened in blood donors including CMV, EBV, parvovirus B-19, and HHV-8 (Kaposi's sarcoma virus);3) establish a repository of linked donor and recipient samples so that any newly emerging infectious agent can be rapidly evaluated for its threat to the blood supply. The risk of these blood transmitted infectious will be assessed by molecular and serologic assays in adult patients at NIH, at Children's National Medical Center and at Suburban Hospital. Blood samples from recipients transfused on one occasion will be obtained pre and 4, 8, 12, and 24 weeks post-transfusion. Recurrently transfused patients will have additional samples at 16 and 20 weeks after the index transfusion and 24 weeks after the last eligible transfusion. After initial infectious disease testing, recipient samples and linked donor samples will be stored in a repository maintained by the National Heart Lung and Blood Institute. The availability of the repository will allow for the assessment of transfusion risk for newly emerging pathogens and also for known agents for which there is no practical assay currently available. For example, this would allow future testing for prions in variant Creutzfeld-Jacob disease (human variant of mad cow disease) or testing for the trypanosome that causes Chagas disease. Informed consent will be obtained to store and later test samples in the repository. Testing will be limited to infectious agents that potentially threaten the blood supply. No genetic testing will be performed. This study has enrolled 1361 patients; 761 from NIH and 600 from Children's National Medical Center. We have complete serial sampling on 896 (65.8%) patients and partial sampling on 159 (11.7%) patients. 296 (21.7%) patients have either died, or were lost to follow up. Ten patients are in active follow up. For the 1055 patients with at least partial sampling, there have been 5439 blood exposures. There has been no transmission of HCV, HBV, HIV or HTLV observed. There is one definite transfusion-related transmission of parvovirus-B-19 in an adult patient representing a per patient risk of 0.1%. There has also been one possible transfusion-related transmission of CMV. A study of microchimerism has shown that donor lymphocytes do not persist in recipients of leukoreduced and irradiated blood products.